小柯机器人

美国普林斯顿大学Mohamed S. Donia研究小组发现，人类微生物组编码抗糖尿病药物阿卡波糖的抗性。相关论文于2021年11月24日在线发表在《自然》杂志上。

利用基于元基因组学的搜索策略，研究人员发现人类肠道和口腔微生物组的细菌成员编码的酶可以选择性地磷酸化临床使用的抗糖尿病药物阿卡波糖，导致其失活。阿卡波糖是人类和细菌α-葡萄糖苷酶的抑制剂，限制了靶标生物代谢复杂碳水化合物的能力。

利用生化检测、X射线晶体学和元基因组分析，研究人员发现，微生物组衍生的阿卡波糖激酶对阿卡波糖具有特异性，为其所在的生物提供了对抗阿卡波糖活性的保护优势，并且广泛存在于西方和非西方人类群体的微生物体中。这些结果提供了一个微生物组对非抗生素药物产生广泛抗性的例子，并表明阿卡波糖抗性已经在人类微生物组中传播，并作为一种防御策略。

据悉，人类微生物组编码了大量的生化酶和途径，其中大部分仍未被描述。

附：英文原文

Title: The human microbiome encodes resistance to the antidiabetic drug acarbose

Author: Balaich, Jared, Estrella, Michael, Wu, Guojun, Jeffrey, Philip D., Biswas, Abhishek, Zhao, Liping, Korennykh, Alexei, Donia, Mohamed S.

Issue&Volume: 2021-11-24

Abstract: The human microbiome encodes a large repertoire of biochemical enzymes and pathways, most of which remain uncharacterized. Here, using a metagenomics-based search strategy, we discovered that bacterial members of the human gut and oral microbiome encode enzymes that selectively phosphorylate a clinically used antidiabetic drug, acarbose1,2, resulting in its inactivation. Acarbose is an inhibitor of both human and bacterial α-glucosidases3, limiting the ability of the target organism to metabolize complex carbohydrates. Using biochemical assays, X-ray crystallography and metagenomic analyses, we show that microbiome-derived acarbose kinases are specific for acarbose, provide their harbouring organism with a protective advantage against the activity of acarbose, and are widespread in the microbiomes of western and non-western human populations. These results provide an example of widespread microbiome resistance to a non-antibiotic drug, and suggest that acarbose resistance has disseminated in the human microbiome as a defensive strategy against a potential endogenous producer of a closely related molecule.

DOI: 10.1038/s41586-021-04091-0

Source: https://www.nature.com/articles/s41586-021-04091-0

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html